Modified oxymatrine as novel therapeutic inhibitors against Monkeypox and Marburg virus through computational drug design approaches.

Global impact of viral diseases specially Monkeypox (mpox) and Marburg virus, emphasizing the urgent need for effective drug interventions. Oxymatrine is an alkaloid which has been selected and modified using various functional groups to enhance its efficacy. The modifications were evaluated using various computatioanal analysis such as pass prediction, molecular docking, ADMET, and molecular dynamic simulation. Mpox and Marburg virus were chosen as target diseases based on their maximum pass prediction spectrum against viral disease. After that, molecular docking, dynamic simulation, DFT, calculation and ADMET prediction were determined. The main objective of this study was to enhance the efficacy of oxymatrine derivatives through functional group modifications and computational analyses to develop effective drug candidates against mpox and Marburg viruses. The calculated binding affinities indicated strong interactions against both mpox virus and Marburg virus. After that, the molecular dynamic simulation was conducted at 100 ns, which confirmed the stability of the binding interactions between the modified oxymatrine derivatives and target proteins. Then, the modified oxymatrine derivatives conducted theoretical ADMET profiling, which demonstrated their potential for effective drug development. Moreover, HOMO-LUMO calculation was performed to understand the chemical reactivity and physicochemical properties of compounds. This computational analysis indicated that modified oxymatrine derivatives for the treatment of mpox and Marburg virus suggested effective drug candidates based on their binding affinity, drug-like properties, stability and chemical reactivity. However, further experimental validation is necessary to confirm their clinical value and efficacy as therapeutic candidates.

Zinc oxide nanoparticles as a novel anticancer approach; in vitro and in vivo evidence.

Currently, the outcomes of conventional chemotherapeutic approaches are unsatisfactory. Clinical application of nanoparticles seems promising. We aim to evaluate the possible antitumor activity of zinc oxide nanoparticles (ZnONPs) as a chemotherapeutic approach in in vitro and in vivo experimental models. An in vitro study was performed on three different cell lines, namely human hepatocellular carcinoma (HEPG2), human prostate cancer (PC3), and none-small cell lung cancer (A549) cell lines. An in vivo study using diethylnitrosamine (DENA)-induced HCC in adult male Wistar rats was conducted to investigate the potential antitumor activity of ZnONPs in HCC and the possible underlying mechanisms. Hepatocellular carcinoma (HCC) was induced by oral administration of DENA given in drinking water (100 mg/L) for 8 weeks. Rats were allocated into four groups, namely a control group, an HCC control group receiving DENA alone, a ZnONPs (10 µg/kg per week, intravenous (i.v.) for 1 month) control group, and a ZnONPs treatment group (receiving ZnONPs + DENA). ZnONPs significantly reduced the elevated serum levels of HCC-related tumor markers alphafetoprotein and alpha-l-fucosidase and the apoptotic marker caspase-3 compared with the untreated HCC rats. In addition, treatment with ZnONPs significantly decreased the elevated levels of hepatocyte integrity and oxidative stress markers as compared with the untreated HCC control group. Furthermore, the histopathological study revealed anaplasia and fibrous degenerations which were significantly corrected by ZnONPs treatment. In conclusion, administration of ZnONPs exhibited a promising preclinical anticancer efficacy in HCC and could be considered as a novel strategy for the treatment HCC in clinical practices.

Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness.

BACKGROUND: KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness. METHODS: We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to study the role of this protein in cell proliferation, migration and apoptosis in vitro. We studied the effects of KIAA1199 knockdown in vivo in two groups of mice (n = 5). We carried out the SILAC LC-MS/MS based proteomic studies on the involvement of KIAA1199 in breast cancer. RESULTS: KIAA1199 mRNA and protein was significantly overexpressed in breast tumor specimens and cell lines as compared with non-neoplastic breast tissues from large-scale microarray and studies of breast cancer cell lines and tumors. To gain deeper insights into the novel role of KIAA1199 in breast cancer, we modulated KIAA1199 expression using shRNA-mediated knockdown in two breast cancer cell lines (MDA-MB-231 and HS578T), expressing higher levels of KIAA1199. The KIAA1199 knockdown cells showed reduced motility and cell proliferation in vitro. Moreover, when the knockdown cells were injected into the mammary fat pads of female athymic nude mice, there was a significant decrease in tumor incidence and growth. In addition, quantitative proteomic analysis revealed that knockdown of KIAA1199 in breast cancer (MDA-MB-231) cells affected a broad range of cellular functions including apoptosis, metabolism and cell motility. CONCLUSIONS: Our findings indicate that KIAA1199 may play an important role in breast tumor growth and invasiveness, and that it may represent a novel target for biomarker development and a novel therapeutic target for breast cancer.

Petunidin attenuates vinclozolin instigated testicular toxicity in albino rats via regulating TLR4/MyD88/TRAF6 and Nrf-2/Keap-1 pathway: A pharmacodynamic and molecular simulation approach.

Vinclozolin (VZN) is a widely used fungicide which exerts deleterious impacts on various organs including testis. Petunidin (PDN) is a polyphenolic compound that demonstrates a broad range of pharmacological activities. Thirty-two rats were divided into 4 groups including the control, VZN (100 mg/kg), VZN (100 mg/kg) + PDN (4 mg/kg) and PDN (4 mg/kg) treated group. The activities of antioxidant enzymes were assessed by using previously documented protocols. The gene expressions were determined by using qRT-PCR. The levels of hepatic function and apoptotic markers were evaluated by using standard ELISA technique. The histological analysis was carried out as per the standard protocol of histology. It was revealed that VZN disrupted the Nrf-2/Keap-1 pathway. Moreover, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme-oxygenase-1 (HO-1) and glutathione reductase (GSR) were reduced whereas levels of reactive oxygen species (ROS) & malondialdehyde (MDA) were promoted following the VZN intoxication. Furthermore, VZN intoxication reduced total sperm count, viability, motility as well as luteinizing hormone (LH), follicle stimulating hormone (FSH), and plasma testosterone. Besides, administration of VZN decreased the expressions of 3ß-Hydroxysteroid dehydrogenase (3ß-HSD), steroidogenic acute regulatory protein (StAR) and 17ß-Hydroxysteroid dehydrogenase (17ß-HSD). Moreover, VZN exposure escalated the expressions of Bcl-2-associated X protein (Bax) and cysteine-aspartic acid protease-3 (Caspase-3) while reducing the expressions of B-cell lymphoma-2 (Bcl-2). Additionally, VZN administration increased the gene expression of toll-like receptor 4 (TLR4), tumor necrosis factor receptor-associated factor 6 (TRAF-6) and myeloid differentiation primary response 88 (MyD88). The levels of interleukin-6 (IL-6), nuclear factor kappa-B (NF-κB), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2) were promoted following the VZN administration. Furthermore, VZN intoxication disrupted the normal histology of testicular tissues. However, VZN + PDN treatment ameliorated testicular damage via regulating aforementioned dysregulations owing to its anti-inflammatory, antioxidative as well as anti-apoptotic potentials. Lastly, molecular docking (MD) was performed to assess the effectiveness of PDN as a curative compound by analyzing its binding affinity with the targeted proteins (Keap1, TLR4 and StAR). Our in-silico evaluations confirmed that PDN possesses the potential to interact with binding pockets of these proteins, emphasizing its capability as a curative compound to mitigate VZN-prompted reproductive damage.

Exploring a novel four-gene system as a diagnostic and prognostic biomarker for triple-negative breast cancer, using clinical variables.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis. This research aims to find real hub genes for prognostic biomarkers of TNBC therapy. The GEO datasets GSE27447 and GSE233242 were analyzed using R package limma to explore DEGs. The PPI was generated using the STRING database. Cytoscape software plug-ins were used to screen the hub genes. Using the DAVID database, GO functional enrichment and KEGG pathway enrichment analysis were performed. Different online expression databases were employed to investigate the functions of real hub genes in tumor driving, diagnosis, and prognosis in TNBC patients with various clinicopathologic characteristics. A total of one hundred DEGs were identified between both datasets. The seven hub genes were identified after the topological parameter analysis of the PPI network. The KEGG pathway and GO analysis suggest that four genes (PSMB1, PSMC1, PSMF1, and PSMD8) are highly enriched in proteasome and were finally considered as real hub genes. Additionally, the expression analysis demonstrated that hub genes were notably up-regulated in TNBC patients compared to controls. Furthermore, correlational analyses revealed the positive and negative correlations among the expression of the real hub genes and various ancillary data, including tumor purity, promoter methylation status, overall survival (OS), genetic alterations, infiltration of CD8+ T and CD4+ immune cells, and a few more, across TNBC samples. Finally, our analysis identified a couple of significant chemotherapeutic drugs, miRNAs and transcription factors (TFS) with intriguing curative potential. In conclusion, we identified four real hub genes as novel biomarkers to overcome heterogenetic-particular challenges in diagnosis, prognosis, and therapy for TNBC patients.

Vitamin C and/or garlic can antagonize the toxic effects of cadmium on growth performance, hematological, and immunological parameters of growing Japanese quail.

This study used 300 1-day-old, sexless, developing chicks of Japanese quail to estimate the ability of vitamin C and/or garlic to antagonize the venomous influence of cadmium (Cd) on the hematological, immunological, and performance characteristics of developing Japanese quail. The quail was separated into 5 similar groups of 60 chicks apiece, and 6 duplicates (10 each) were given to each sub-group. The control group received a basal diet without any supplements. The Cd group was nourished with a basal diet of + 80 mg cadmium chloride (CdCl2)/kg diet. The 3rd group was fed a basal diet + 80 mg CdCl2/kg diet and complemented with a 200 mg Vitamin C (Cd + C)/kg diet. The 4th group was nourished with a basal diet + 80 mg CdCl2/kg diet and complemented by a 500 mg dried garlic powder (Cd + G)/kg diet. The 5th group was fed a basal diet + 80 mg CdCl2/kg diet, complemented by a 200 mg vitamin C/kg diet + 500 mg dried garlic powder (Cd + CG)/kg diet. Results showed that in the 5th group in which cadmium was added together with Vit C + garlic, there was an improvement in both live weight gain (1-42 d) and feed consumption (1-21 and 1-42 d ) compared to the group in which Cd was added alone. The addition of Vit C alone and together with garlic seems to completely improve the cadmium-related increase in alkaline phosphatase (ALP), and Aspartate aminotransferase (AST), and Malondialdehyde (MDA) levels when compared to the control. Compared to cadmium-polluted diets, quail that got cadmium and feed additives significantly reduced cadmium residue. In addition, the cadmium group's serum immunoglobulin M (IgM) level decreased significantly. These data imply that dietary supplementation with (C) or (G) may be beneficial in retrogressing the drop in immunoglobulin G (IgG) and IgM caused by Cd and minimizing Cd's deleterious influence on immunity.

Evaluation of the effect of COVID-19 mandated shift to virtual teaching on medical students' performance at King Khalid University, Abha.

Objectives: The rapid spread of the COVID-19 pandemic required populations in most parts of the world to take drastic precautions. Face-to-face teachings were suspended, and the teaching and learning process was shifted to the virtual mode. This was a formidable challenge for students, teachers, parents, guardians, and academic administrators. The main objective of this study was to assess the impact of the shift to virtual mode on medical students' academic performance in general and systemic pathology courses. Methods: The grades achieved in a quiz and practical test taken before the shift to virtual classes were compared to another quiz and practical exam taken by the same groups of students after several weeks of virtual teaching. The paired t-test was conducted to test the hypotheses, and SPSS software was used for data analyses. A short electronic survey was designed and sent to the targeted students (N = 103). The targeted students were also surveyed to understand their experience with e-learning during this time. Results: In total, 60% of the students reported their e-learning experience as valuable, and 84% prefer to have e-learning as part of the teaching and learning process even after normalcy is restored. The students' performance in the post-virtual tests was significantly better than that in the pre-virtual tests. Conclusion: The virtual learning format was well received by the students and influenced their academic outcomes. Institutes should provide training sessions for staff and students to address potential education drawbacks and provide modern educational technologies and simulation labs to enhance the educational systems.

Ranking Breast Cancer Drugs and Biomarkers Identification Using Machine Learning and Pharmacogenomics.

Breast cancer is one of the major causes of death in women worldwide. It is a diverse illness with substantial intersubject heterogeneity, even among individuals with the same type of tumor, and customized therapy has become increasingly important in this sector. Because of the clinical and physical variability of different kinds of breast cancers, multiple staging and classification systems have been developed. As a result, these tumors exhibit a wide range of gene expression and prognostic indicators. To date, no comprehensive investigation of model training procedures on information from numerous cell line screenings has been conducted together with radiation data. We used human breast cancer cell lines and drug sensitivity information from Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases to scan for potential drugs using cell line data. The results are further validated through three machine learning approaches: Elastic Net, LASSO, and Ridge. Next, we selected top-ranked biomarkers based on their role in breast cancer and tested them further for their resistance to radiation using the data from the Cleveland database. We have identified six drugs named Palbociclib, Panobinostat, PD-0325901, PLX4720, Selumetinib, and Tanespimycin that significantly perform on breast cancer cell lines. Also, five biomarkers named TNFSF15, DCAF6, KDM6A, PHETA2, and IFNGR1 are sensitive to all six shortlisted drugs and show sensitivity to the radiations. The proposed biomarkers and drug sensitivity analysis are helpful in translational cancer studies and provide valuable insights for clinical trial design.

Pathological and genetic characterization of foot and mouth disease viruses collected from cattle and water buffalo in Egypt.

Foot-and-mouth disease (FMD), a highly contagious viral disease caused by FMD virus (FMDV) that threatens Egypt's livestock industry. FMDV causes severe economic losses in the livestock, with restriction of international trade from endemic regions. Surveillance for FMDV serotypes circulating in Egypt is urgently needed to assess the epidemiological situation in the country. FMD outbreaks reported in Egypt in between December 2016 and January-March 2017. A cross-sectional study was conducted to identify the FMDV serotypes responsible for the outbreaks and to collect information on the virus's morphopathological effects. Postmortem tissue and clinical samples (oral swabs, vesicular fluids from ruptured vesicles, and blood) were collected from recently deceased and infected animals. Pathological examination revealed classical FMD lesions as vesicular and erosive lesions on epithelial tissues with non-suppurative lymphoplasmacytic myocarditis. Phylogenetic and sequencing analyses demonstrated that FMDV serotype O, EA-3 topotype, VP1 is the prevalent serotype responsible for the pathological alterations and the high mortality in young calves, adult cattle, and water buffalo. The outcomes indicate continuous mutations in the circulating FMDV, which result in the occasional failure of vaccination. Based on these findings, extensive continuous monitoring and serotyping of the existing circulating FMDV isolates and regular vaccination with reevaluation of the currently used vaccine in Egypt are recommended to prevent the recurrence of such outbreaks.

Integration of Ultrastructural and Computational Approaches Reveals the Protective Effect of Astaxanthin against BPA-Induced Nephrotoxicity.

BACKGROUND: Bisphenol A (BPA) is an environmental contaminant that can induce deleterious organ effects. Human Cytochrome P450 CYP2C9 enzyme belongs to the essential xenobiotic-metabolizing enzymes, producing ROS as a byproduct. Astaxanthin (ATX) is a powerful antioxidant that protects organs and tissues from the damaging effects of oxidative stress caused by various diseases. AIM OF THE STUDY: This study investigated the possible protective impacts of ATX against BPA-induced nephrotoxicity and its underlying mechanism. MATERIALS AND METHODS: Kidney tissues were isolated and examined microscopically from control, protected, and unprotected groups of rats to examine the potential protective effect of ATX against nephrotoxicity. Moreover, a molecular dynamic (MD) simulation was conducted to predict the performance of ATX upon binding to the active site of P450 CYP2C9 protein receptor as a potential mechanism of ATX protective effect. RESULTS: Implemented computational methods revealed the possible underlying mechanism of ATX protection; the protective impact of ATX is mediated by inhibiting P450 CYP2C9 through binding to its dimeric state where the RMSF value for apo-protein and ATX-complex system were 5.720.57 and 1.040.41, respectively, implicating the ATX-complex system to have lesser variance in its residues, leading to the prevention of ROS excess production, maintaining the oxidant-antioxidant balance and re-establishing the proper mitochondrial functionality. Furthermore, the experimental methods validated in silico outcomes and revealed that ATX therapy effectively restored the typical histological architecture of pathological kidney tissues. CONCLUSIONS: ATX prevents BPA-induced nephrotoxicity by controlling oxidative imbalance and reversing mitochondrial dysfunction. These outcomes shed new light on the appropriate use of ATX as a treatment or prophylactic agent for these severe conditions.

Influence of dietary mannan-oligosaccharides supplementation on hematological characteristics, blood biochemical parameters, immune response and histological state of laying hens.

This study aimed to determine the influence of dietary mannan-oligosaccharides (MOS) on the immune system, hematological traits, blood biochemical parameters, and histological state of laying hens. At 34 wk of age, The Mandarah chicken strain's 120 laying hens and 12 cocks were divided into 4 groups, each with 30 hens and 3 cocks. The first group performed as a control group, which nourished on a basal diet. The second, third, and fourth experimental groups received 0.1, 0.2, and 0.5 g/kg of MOS and a base diet, respectively. Birds obtained MOS at numerous doses significantly (P ˂ 0.05) raised serum levels of immunoglobulin Y (IgY), immunoglobulin M (IgM), and avian influenza (AI) antibodies compared to control birds. Furthermore, adding MOS at a level of 0.1 g/kg diet significantly improved the immune response of the control group. Additionally, compared to the control group, treated birds with MOS at various dosages did not significantly enhance hematological parameters such as red blood cells (RBCs), white blood cells (WBCs), hemoglobin, and hematocrit. Compared to control birds, birds fed MOS at all levels exhibited considerably lower serum cholesterol, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) values. Also, compared to other treated birds, MOS-treated birds displayed improved histological examination of the small intestine, isthmus, and testis compared to the control group, particularly in birds fed MOS at 0.1 and 0.2 g/kg diet. It could be concluded that using MOS at 0.1 or 2 g/kg diet can successfully improve the physiological performance and overall health of laying hens.

Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy.

Epithelial cell transforming 2 (ECT2) is a potential oncogene and a number of recent studies have correlated it with the progression of several human cancers. Despite this elevated attention for ECT2 in oncology-related reports, there is no collective study to combine and integrate the expression and oncogenic behavior of ECT2 in a panel of human cancers. The current study started with a differential expression analysis of ECT2 in cancerous versus normal tissue. Following that, the study asked for the correlation between ECT2 upregulation and tumor stage, grade, and metastasis, along with its effect on patient survival. Moreover, the methylation and phosphorylation status of ECT2 in tumor versus normal tissue was assessed, in addition to the investigation of the ECT2 effect on the immune cell infiltration in the tumor microenvironment. The current study revealed that ECT2 was upregulated as mRNA and protein levels in a list of human tumors, a feature that allowed for the increased filtration of myeloid-derived suppressor cells (MDSC) and decreased the level of natural killer T (NKT) cells, which ultimately led to a poor prognosis survival. Lastly, we screened for several drugs that could inhibit ECT2 and act as antitumor agents. Collectively, this study nominated ECT2 as a prognostic and immunological biomarker, with reported inhibitors that represent potential antitumor drugs.

A Comprehensive Pan-Cancer Analysis Identifies CEP55 as a Potential Oncogene and Novel Therapeutic Target.

Emerging research findings have shown that a centrosomal protein (CEP55) is a potential oncogene in numerous human malignancies. Nevertheless, no pan-cancer analysis has been conducted to investigate the various aspects and behavior of this oncogene in different human cancerous tissues. Numerous databases were investigated to conduct a detailed analysis of CEP55. Initially, we evaluated the expression of CEP55 in several types of cancers and attempted to find the correlation between that and the stage of the examined malignancies. Then, we conducted a survival analysis to determine the relationship between CEP55 overexpression in malignancies and the patient's survival. Furthermore, we examined the genetic alteration forms and the methylation status of this oncogene. Additionally, the interference of CEP55 expression with immune cell infiltration, the response to various chemotherapeutic agents, and the putative molecular mechanism of CEP55 in tumorigenesis were investigated. The current study found that CEP55 was upregulated in cancerous tissues versus normal controls where this upregulation was correlated with a poor prognosis in multiple forms of human cancers. Additionally, it influenced the level of different immune cell infiltration and several chemokines levels in the tumor microenvironment in addition to the response to several antitumor drugs. Herein, we provide an in-depth understanding of the oncogenic activities of CEP55, identifying it as a possible predictive marker as well as a specific target for developing anticancer therapies.

Exploration of Potent Antiviral Phytomedicines from Lauraceae Family Plants against SARS-CoV-2 Main Protease.

A new Coronaviridae strain, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), emerged from Wuhan city of China and caused one of the substantial global health calamities in December 2019. Even though several vaccines and drugs have been developed worldwide since COVID-19, a cost-effective drug with the least side effects is still unavailable. Currently, plant-derived compounds are mostly preferred to develop antiviral therapeutics due to its less toxicity, easy access, and cost-effective characteristics. Therefore, in this study, 124 phytochemical compounds from plants of Lauraceae family with medicinal properties were virtually screened against SARS-CoV-2 Mpro. Identification of four phytomolecules, i.e., cassameridine, laetanine, litseferine and cassythicine, with docking scores -9.3, -8.8, -8.6, and -8.6 kcal/mol, respectively, were undertaken by virtual screening, and molecular docking. Furthermore, the molecular dynamic simulation and essential dynamics analysis have contributed in understanding the stability and inhibitory effect of these selected compounds. These phytomolecules can be considered for further in vitro and in vivo experimental study to develop anti-SARS-CoV-2 therapeutics targeting the main protease (Mpro).

Signet ring cell component predicts the response to neoadjuvant chemoradiotherapy in rectal cancer. Long interim results of a single institution experience.

There are limited studies evaluating the correlation between the presence of signet ring carcinoma and tumor response to neoadjuvant therapy in the rectum. Hereby, we aimed to report for the first time our experience from Upper Egypt through assessing the predictive role of signet ring cell component (SRCC) in the response to preoperative chemoradiotherapy (PCRT) and the impact of histological types (SRCC versus other types) on survival. This retrospective study analysed the medical records of 195 patients with locally advanced rectal cancer treated from 2011, to 2018. Patients were divided into two groups according to histological types: SRCC group and non SRCC group. All patients received PCRT followed by surgery. SRCC group was associated with significant higher rate of complete clinical response (cCR) and pathologic complete response (pCR) (83.3% and 88.9% respectively) as compared to non SRCC group (9.0% and 10.2% respectively); P<0.0001. Fifteen cases (93.8%) who were diagnosed by magnetic resonance tumor regression grade (mrTRG) and diffusion weighted imaging (DWI) as cCR after PCRT, also achieved pCR, in contrast to 88.9% of cases without SRCC. Signet ring histology was the only predictor of pCR in multivariate analysis (P=0.027). There was no statistically significant difference between both histological groups as regard to survival. SRCC is an important predictor of pCR and assessing their response to PCRT using mrTRG and DWI showed high sensitivity for the detection of cCR, making them good candidates for watch-and-wait approach. Histological types did not significantly affect the survival outcome.

A conflicts' classification for IoT-based services: a comparative survey.

Recently, Internet of Things (IoT)-based systems, especially automation systems, have become an indispensable part of modern-day lives to support the controlling of the networked devices and providing context-aware and intelligent environments. IoT-based services/apps developed by the end-users interact with each other and share concurrent access to devices according to their preferences, which increases safety, security, and correctness issues in IoT systems. Due to the critical impacts resulting from these issues, IoT-based apps require a customized type of compilers or checking tools that capable of analyzing the structures of these apps and detecting different types of errors and conflicts either in intra-IoT app instructions or in inter-IoT apps interactions. A plethora of approaches and frameworks have been proposed to assist the best practices for end-users in developing their IoT-based apps and mitigate these errors and conflicts. This paper focuses on conflict classification and detection approaches in the context of IoT systems by investigating the current research techniques that provided conflicts' classification or detection in IoT systems (published between 2014 and 2020). A classification of IoT-based apps interaction conflicts is proposed. The proposed conflicts' classification provides a priori conflicts detection method based on the analysis of IoT app instructions' relationships with utilizing the state-of-the-art Satisfiability Modulo Theories (SMT) model checking and formal notations. The current detection approaches are compared with each other according to the proposed conflicts' classification to determine to which extend they cover different conflicts. Based on this comparison, we provide evidence that the existing approaches have a gap in covering different conflicts' levels and types which yields to minimize the correctness and safety of IoT systems. We point out the need to develop a safety and security compiler or tool for IoT systems. Also, we recommend using a hybrid approach that combines model checking with a variety of languages and semantic technologies in developing future IoT-based apps verification frameworks to cover all levels and types of conflicts to guarantee and increase the safety, security, and correctness of IoT systems.

May-Thurner Compressive Syndrome Unmasked by Rapid Weight Loss.

Description May-Thurner Syndrome (MTS) is an anatomical syndrome characterized by a predisposition to clot formation when there is compression of the left iliac vein by the right iliac artery. In this case, we discuss an atypical presentation of MTS in a young male after rapid weight loss. The patient was admitted for an unprovoked massive proximal deep vein thrombosis (DVT) after a two-hundred-pound weight loss during the preceding six-month period. Treatment involved mechanical thrombectomy by interventional radiology, initiation of apixaban and recommended follow up with vascular surgery for angioplasty instead of immediate stent placement.

The chemopreventive effect of thymol against dimethylhydrazine and/or high fat diet-induced colon cancer in rats: Relevance to NF-κB.

AIM: Evaluating the possible protective effect of thymol as an approach against 1,2 N,N-dimethylhydrazine and/or high-fat diet (HFD)-induced colon cancer. MAIN METHODS: Adult male Wistar rats were divided into 7 groups, namely a normal control group, colon cancer groups received DMH (40 mg/kg i.p., twice weekly), 20% HFD and DMH/HFD, thymol (20 mg/kg/day, p.o.), thymol/DMH and thymol/DMH/HFD (treatment of all groups continued for 16 weeks). KEY FINDINGS: Thymol significantly reduced the elevated serum levels of colon related tumor markers carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) as well as the apoptotic marker, caspase-3 compared with the colon cancer group. In addition, it mitigated colonic tissue oxidative stress markers and inflammatory mediators. Moreover, the histopathological study revealed reduction of mucous secretion with elongated nuclei, frequent mitotic figures, focal nuclear stratification, mild interstitial edema, and markedly dilated congested blood vessels, aberrant crypt foci (ACF); adenoma with moderate to severe dysplasia of colon corrected by thymol treatment. SIGNIFICANCE: The administration of thymol had a promising preclinical protective efficacy and could be considered as a new strategy for the prophylaxis from colon cancer in clinical practices.

Impaired Baseline Renal Function May Not Influence Outcomes and Survival After Left Ventricular Assist Device Implantation.

BACKGROUND: We investigated changes in estimated glomerular filtration rate (eGFR) after left ventricular assist device (LVAD) implant and the impact on long-term outcomes. METHODS: A retrospective analysis was conducted for 255 patients with LVADs, divided into 2 groups based on preimplant eGFR (<60 or >60 mL/min/1.73 m2) and into 6 grades (grade 1, >90 mL/min/1.73 m2 normal; grade 2, 60-89 mild dysfunction; grade 3, 45-59 moderate; grade 4, 30-44 moderate to severe; grade 5, 15-29 severe; or grade 6, <15 kidney failure). Changes in eGFR and the impact on long-term outcome and survival were analyzed. RESULTS: One-month postimplant eGFR of the total cohort increased from a baseline of 75.19 ± 34.35 to 118.97 ± 67.62 mL/min/1.73 m2(P < .001). eGRF 4 years postimplant was higher than baseline but not significantly (P = .48). Patients with a preimplant eGFR > 60 followed the same pattern as the entire cohort. The preimplant eGFR < 60 group had a significant increase at 1 month (P < .001), eGFR remained significantly higher than baseline 4 years postimplant (P = .032), and there was a sustained transition to improved distribution of renal function grade after LVAD implant. Post-LVAD implant survival at 1, 3, and 5 years for baseline eGFR > 60 was 76%, 54%, and 48% and for eGFR < 60 was 71%, 60%, and 48%, respectively (P = .92). CONCLUSIONS: Patients with a low preimplant eGFR derive benefit from LVAD therapy, with eGFR remaining elevated above preimplant levels. Preimplant renal dysfunction did not impact negatively on long-term morbidity and mortality.

Automated language essay scoring systems: a literature review.

BACKGROUND: Writing composition is a significant factor for measuring test-takers' ability in any language exam. However, the assessment (scoring) of these writing compositions or essays is a very challenging process in terms of reliability and time. The need for objective and quick scores has raised the need for a computer system that can automatically grade essay questions targeting specific prompts. Automated Essay Scoring (AES) systems are used to overcome the challenges of scoring writing tasks by using Natural Language Processing (NLP) and machine learning techniques. The purpose of this paper is to review the literature for the AES systems used for grading the essay questions. METHODOLOGY: We have reviewed the existing literature using Google Scholar, EBSCO and ERIC to search for the terms "AES", "Automated Essay Scoring", "Automated Essay Grading", or "Automatic Essay" for essays written in English language. Two categories have been identified: handcrafted features and automatically featured AES systems. The systems of the former category are closely bonded to the quality of the designed features. On the other hand, the systems of the latter category are based on the automatic learning of the features and relations between an essay and its score without any handcrafted features. We reviewed the systems of the two categories in terms of system primary focus, technique(s) used in the system, the need for training data, instructional application (feedback system), and the correlation between e-scores and human scores. The paper includes three main sections. First, we present a structured literature review of the available Handcrafted Features AES systems. Second, we present a structured literature review of the available Automatic Featuring AES systems. Finally, we draw a set of discussions and conclusions. RESULTS: AES models have been found to utilize a broad range of manually-tuned shallow and deep linguistic features. AES systems have many strengths in reducing labor-intensive marking activities, ensuring a consistent application of scoring criteria, and ensuring the objectivity of scoring. Although many techniques have been implemented to improve the AES systems, three primary challenges have been identified. The challenges are lacking of the sense of the rater as a person, the potential that the systems can be deceived into giving a lower or higher score to an essay than it deserves, and the limited ability to assess the creativity of the ideas and propositions and evaluate their practicality. Many techniques have only been used to address the first two challenges.